The specific aims of the research plan are: 1. To test the hypothesis that potassium is recycled in the renal medulla. Projects include: a. potassium secretion in the pars recta and descending limb and the role of Na-K-ATPase; b. potassium reabsorption by the outer medullary collecting duct in vivo; c. the effect of potassium recycling on sodium, chloride and potassium reabsorption by the thick ascending limb in the normal kidney and in chronic renal failure. 2. To study the microcirculation of the medulla. Projects include: a. intravascular regulatory factors (the relationship between erythrocyte and blood velocity, and the geometry of vasa recta); b. extravascular regulatory factors (antidiuretic hormone, carbon dioxide tension, and intermittent blood flow); c. determinants of transcapillary fluid exchange (effect of blood flow, and membrane transport properties of vasa recta). 3. To study the urinary concentrating mechanism. Projects include: a. the role of the pelvic ureter; b. the role of the thin loops of Henle. 4. To characterize the transport mechanisms of renal epithelial cells grown in tissue culture. Investigations of tubule and epithelial function will be performed with the aid of micropuncture, microperfusion, electrophysiological, microanalytical and microenzymatic techniques and the new Stanford JEOL electron microprobe. Studies of medullary capillary blood flow will be performed with the aid of videomicroscopy, fluorescence illumination, computer-assisted photoanalyzer, and morphometric techniques. An unusual aspect of the research is the continued close collaboration between a physiologist and a chemical engineer and their associates. The long-term objective of this laboratory is to elucidate the function of the renal medulla and thereby provide a basis for understanding the nature and consequences of disordered medullary function, which frequently occurs in kidney disease.